Asthma is a significant health problem worldwide and Allergic Bronchopulmonary aspergillosis (ABPA) complicates the course of 1-2% of patients of asthma. Aspergillus skin hypersensitivity (AH) is the first step for diagnosis of ABPA. This study was conducted to know the correlation of AH with severity and duration of asthma. Patients, age >15 years, of asthma attending this hospital from January 2015 to December 2015 were included. Asthma was diagnosed clinically and confirmed with spirometry. Of 282 patients 206 patients were AH positive. The AST-positivity in patients having severe asthma (96.8%) was higher than that in patients having mild (36.8%) and moderate asthma (80.4%). The median (IQR) duration of asthma of AH positive patients was 5.0 yrs. This study emphasized the need of ABPA screening by intradermal skin test especially in patients having severe asthma and/or those having asthma for longer duration in order for early diagnosis of ABPA.

Severe asthma is a heterogeneous disease entity to which diverse cellular components and pathogenetic mechanisms contribute. Current asthma therapies, including new biologic agents, are mainly target...

Severe asthma is a heterogeneous disease entity to which diverse cellular components and pathogenetic mechanisms contribute. Current asthma therapies, including new biologic agents, are mainly targeting T helper type 2 cell-dominant inflammation, so that they are often unsatisfactory in the treatment of severe asthma. Respiratory fungal exposure has long been regarded as a precipitating factor for severe asthma phenotype. Moreover, as seen in clinical definitions of allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS), fungal allergy-associated severe asthma phenotype is increasingly thought to have distinct pathobiologic mechanisms requiring different therapeutic approaches other than conventional treatment. However, there are still many unanswered questions on the direct causality of fungal sensitization in inducing severe allergic inflammation in SAFS. Recently, growing evidence suggests that stress response from the largest organelle, endoplasmic reticulum (ER), is closely interconnected to diverse cellular immune/inflammatory platforms, thereby being implicated in severe allergic lung inflammation. Interestingly, a recent study on this issue has suggested that ER stress responses and several associated molecular platforms, including phosphoinositide 3-kinase-δ and mitochondria, may be crucial players in the development of severe allergic inflammation in the SAFS. Defining emerging roles of ER and associated cellular platforms in SAFS may offer promising therapeutic options in the near future.

Aspergillus fumigatus is the most prevalent filamentous fungal pathogen of humans, causing either severe allergic bronchopulmonary aspergillosis or often fatal invasive pulmonary aspergillosis (IPA) in individuals with hyper- or hypo-immune deficiencies, respectively. Disease is primarily initiated upon the inhalation of the ubiquitous airborne conidia-the initial inoculum produced by A. fumigatus-which are complete developmental units with an ability to exploit diverse environments, ranging from agricultural composts to animal lungs. Upon infection, conidia initially rely on their own metabolic processes for survival in the host's lungs, a nutritionally limiting environment. One such nutritional limitation is the availability of aromatic amino acids (AAAs) as animals lack the enzymes to synthesize tryptophan (Trp) and phenylalanine and only produce tyrosine from dietary phenylalanine. However, A. fumigatus produces all three AAAs through the shikimate-chorismate pathway, where they play a critical role in fungal growth and development and in yielding many downstream metabolites. The downstream metabolites of Trp in A. fumigatus include the immunomodulatory kynurenine derived from indoleamine 2,3-dioxygenase (IDO) and toxins such as fumiquinazolines, gliotoxin, and fumitremorgins. Host IDO activity and/or host/microbe-derived kynurenines are increasingly correlated with many Aspergillus diseases including IPA and infections of chronic granulomatous disease patients. In this review, we will describe the potential metabolic cross talk between the host and the pathogen, specifically focusing on Trp metabolism, the implications for therapeutics, and the recent studies on the coevolution of host and microbe IDO activation in regulating inflammation, while controlling infection.

Patients with cystic fibrosis (CF) experience chronic or recurrent bacterial and fungal lung infections. Many patients with CF cannot effectively clear Aspergillus from their lungs. This may result i...

CONCLUSIONS: Prednisolone was more effective in inducing response than itraconazole in acute-stage ABPA. However, itraconazole was also effective in a considerable number and, with fewer side effects compared with prednisolone, remains an attractive alternative in the initial treatment of ABPA.

Vitamin D deficiency is believed to a pathogenetic factor in patients with allergic bronchopulmonary aspergillosis (ABPA) and cystic fibrosis. Whether vitamin D deficiency is also prevalent in ABPA c...

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Vitamin D deficiency is believed to a pathogenetic factor in patients with allergic bronchopulmonary aspergillosis (ABPA) and cystic fibrosis. Whether vitamin D deficiency is also prevalent in ABPA complicating asthma, remains unknown. Herein, we evaluate vitamin D levels in asthmatic patients with and without ABPA. In a prospective study, plasma vitamin D (25[OH]D) levels were measured in consecutive subjects with asthma (n=75), ABPA (n=158) and healthy volunteers (n=50). Vitamin D levels <20 ng/mL were considered as vitamin D deficiency. There was no difference in mean (95% CI) vitamin D levels between healthy controls (15.3 [12.7-17.9]), asthmatics (19.2 [16.3-22.1]) and subjects with ABPA (18.9 [16.9-20.8]) (p=0.22). Vitamin D deficiency was encountered in 70%, 64% and 65% of the healthy controls, asthmatics and ABPA subjects, respectively, and was not different between the groups (p=0.79). There was no difference in the asthma control, pulmonary function, immunological findings and the severity of bronchiectasis, in patients with ABPA, with and without vitamin D deficiency. Vitamin D deficiency is equally prevalent in asthmatic patients with or without ABPA in the Indian subcontinent, and does not appear to play a major role in the pathogenesis of ABPA complicating asthma. This article is protected by copyright. All rights reserved.

Although the spectrum of fungal pathology has been studied extensively in immunosuppressed patients, little is known about the epidemiology, risk factors, and management of fungal infections in chron...

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Although the spectrum of fungal pathology has been studied extensively in immunosuppressed patients, little is known about the epidemiology, risk factors, and management of fungal infections in chronic pulmonary diseases like bronchiectasis. In bronchiectasis patients, deteriorated mucociliary clearance-generally due to prior colonization by bacterial pathogens-and thick mucosity propitiate, the persistence of fungal spores in the respiratory tract. The most prevalent fungi in these patients are Candida albicans and Aspergillus fumigatus; these are almost always isolated with bacterial pathogens like Haemophillus influenzae and Pseudomonas aeruginosa, making very difficult to define their clinical significance. Analysis of the mycobiome enables us to detect a greater diversity of microorganisms than with conventional cultures. The results have shown a reduced fungal diversity in most chronic respiratory diseases, and that this finding correlates with poorer lung function. Increased knowledge of both the mycobiome and the complex interactions between the fungal, viral, and bacterial microbiota, including mycobacteria, will further our understanding of the mycobiome's relationship with the pathogeny of bronchiectasis and the development of innovative therapies to combat it.

CONCLUSIONS: This study suggests that omalizumab might be an interesting therapeutic strategy in ABPA, associated with less side effects compared to long-term corticosteroids. Further randomized-controlled trials are needed to ascertain the efficacy of omalizumab in CF patients with ABPA.